The long term aim of this work is to obtain information about the control of proliferation and differentiation in epithelia of the oral mucosa which will lead to a greater understanding of the proliferative malfunction in various oral diseases. Such information would also enable the manipulation of cell populations to therapeutic advantage. Stem cells appear to be responsible for cell renewal throughout the life of an organism and are the cells most at risk from neoplastic transformation, i.e., are carcinogen target cells. Stem cells probably represent only a small proportion of the cells within a tissue and thus the study of gross reactions to growth factors or cytotoxic insult may be misleading as the response so observed is largetly that of the amplifying cells which are transitory within the tissue. We aim to establish clonal culture systems for oral epithelia of both mouse and man. These will be studied using cell kinetic and radiobilogical techniques in order to identify and characterize the stem cell and amplifying cell populations within these tissues. We will study the effects of Epidermal Growth Factor, (which may itself, or molecules like it, be an important physiological regulator in vivo), on the growth of oral keractinocytes. Tumor promoters play a major part in carcinogenesis and induce gross changes in kerationocyte growth: we will study the way in which promoters can modulate cell proliferation in vitro. As stem cells are believed to play a major role during the recovery of tissues from radiation damage, alterations in the growth and proliferative subpopulations of irradiated epithelia and epithelial cultures will also be examined. The in vitro data so produced by these various approaches, from mouse and man, combined with published in vivo data (largely from mouse), would be used to produce an analysis of the human in vivo situation.